Nitrate, Brain Insulin-sensitivity, Vascular Function
Conditions
Brief summary
Disturbances in brain insulin-sensitivity are not only observed in abdominal obesity and type 2 diabetes mellitus (T2D), but also during brain aging and in dementia. Inorganic nitrate may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally administered insulin, through beneficial effects on brain vascular function. Therefore, we now hypothesize that inorganic nitrate, which can be found in several vegetables such as beetroot, improves brain insulin-sensitivity, as assessed by the gray-matter CBF response to intranasally administered insulin, in abdominally obese men.
Interventions
DIETARY_SUPPLEMENTPotassium nitrate
Acute intervention (5.5 hours)
DIETARY_SUPPLEMENTPlacebo
Acute intervention (5.5 hours)
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Men; * Aged between 18 - 60 years; * Waist circumference \> 102 cm (abdominally obese); * Fasting plasma glucose ≤ 7.0 mmol/L; * Fasting serum total cholesterol ≤ 8.0 mmol/L; * Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 100 mmHg; * Stable body weight (weight gain or loss \< 3 kg in the past three months); * Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study; * Willingness not to use antibacterial mouth wash or toothpaste, chewing-gum and tongue-scraping a week before the study; * No difficult venipuncture as evidenced during the screening visit.
Exclusion criteria
* Women; * Left-handedness; * Current smoker, or smoking cessation \< 12 months; * Diabetic patients; * Familial hypercholesterolemia; * Abuse of drugs; * More than 3 alcoholic consumptions per day; * Use of products or dietary supplements known to interfere with the main outcomes as judged by the principal investigators; * Use medication to treat blood pressure, lipid or glucose metabolism; * Pharmacological treatment advised based on the Dutch general practitioners' association (NHG) for cardiovascular risk management; * Use of an investigational product within another biomedical intervention trial within the previous 1-month; * Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis; * Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident; * Specific contra-indications for MRI imaging, including pacemakers, surgical clips/material in body, metal splinters in eye, claustrophobia, or tattoos in the facial area, such as permanent make-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain insulin sensitivity | Change from placebo intervention at 2 hours after supplement intake | MRI arterial spin labeling, cerebral blood flow measurements before and after a nasal insulin spray |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular function markers | Change from fasting at 4 hours after supplement intake | Flow-mediated vasodilation (FMD) of the brachial and femoral artery |
| Cold pressure test | Change from placebo at 4 hours after supplement intake | Carotid artery response to cold pressure test |
| Cardiometabolic risk markers (1) | Change from placebo at 4 hours after supplement intake | Plasma markers for low-grade systemic inflammation (CRP) |
| Cardiometabolic risk markers (2) | Change from placebo at 4 hours after supplement intake | Plasma marker for endothelial dysfunction (NOx) |
| Brain vascular function | Change from placebo intervention at 2 hours after supplement intake | MRI arterial spin labeling, cerebral blood flow measurements |
| Cardiometabolic risk markers (4) | During the 5.5 hours following supplement intake | Plasma brain derived neurotrophic factor (BDNF) |
| Postprandial metabolism (1) | During the 5.5 hours following supplement intake | Serum lipid metabolism |
| Postprandial metabolism (2) | During the 5.5 hours following supplement intake | Plasma glucose metabolism |
| Cardiometabolic risk markers (3) | Change from placebo at 4 hours after supplement intake | Office blood pressure |
Countries
Netherlands
Outcome results
None listed